Numerous active pharmaceutical ingredients (API) are know to be incompatible with the acidic environment present in mammalian, such as human, stomachs. Due to this incompatibility, it can be advantageous to protect these acid-labile compounds until such time as they reach a point in the GI tract having a pH which is more compatible with the particular API. Controlled or delayed release pharmaceutical compositions for acid-labile drugs, in particular for acid-labile drugs that need to be delivered to the upper intestine of a mammal and where exposure of the acid-labile API to the acidic gastric environment is to be avoided, is often desirable.
One such acid-labile API which is advantageously delivered to the human duodenum is pancreatin. Pancreatin is a substance which is derived from mammalian pancreas glands and comprises different digestive enzymes such as lipases, amylases and proteases. Pancreatin has been used to treat pancreatic exocrine insufficiency (PEI) which is often associated with cystic fibrosis, chronic pancreatitis, post-pancreatectomy, post-gastrointestinal bypass surgery (e.g. Billroth II gastroenterostomy) and ductal obstruction from neoplasm (e.g. of the pancreas or common bile duct). Pancreatin microspheres are the treatment of choice for diseases or disorders caused by digestive enzyme deficiency in mammals such as humans. This is due to the fact that high-performance pancreatin microsphere products like Creon™ provide a therapeutically effective load of active enzymes while at the same time providing properly sized microspheres capable of targeting the optimal location in the digestive tract where digestive enzyme activity will be needed, in particular the upper intestine such as the duodenum.
Recently, governmental health authorities have initiated a reassessment of the compatibility of certain pharmaceutical excipients which had previously been used in the formulation of pancreatin-containing products and have provided advice concerning the use of specific pharmaceutical excipients such as mineral oil (see e.g. US Code of Federal Regulations, 21 CFR §201.302) and dibutyl phthalate (see e.g. directive 2003/36/EC of the European Parliament and the Council of 26 May 2003 amending for the 25th time Council Directive 76/769/EEC). As a result, it is now recommended that mineral oil not be provided indiscriminately to either pregnant women or infants. Similarly, health authorities today recommend restricting the use of dibutyl phthalate. Therefore, a need exists to provide patients with formulations of pharmaceutical products which would be responsive to the current advice of health authorities.
Some controlled release pharmaceutical preparations and/or methods for preparing them are disclosed in EP 0063014 or U.S. Pat. No. 5,725,880.
Pharmaceutical preparations which may comprise pancreatin and an enteric coating are disclosed in DE 19907764; EP 0021129 (U.S. Pat. No. 4,280,971); EP 0035780; EP 0583726 (U.S. Pat. No. 5,378,462); U.S. Pat. No. 5,225,202; U.S. Pat. No. 5,750,148; U.S. Pat. No. 6,224,910; US 2002/0146451 and WO 02/40045.
U.S. Pat. No. 4,786,505 discloses pharmaceutical preparations for oral use.
Published patent application US 2004/0213847 discloses delayed release pharmaceutical compositions containing proton pump inhibitors.
Published patent application US 2002/061302 discloses the use of physiologically acceptable enzyme mixtures for the treatment of diabetes.